Favourable melanoma prognosis associated with the expression of the tumour necrosis factor receptor and the alpha1beta1 integrin: a preliminary report.
Recently we encountered a patient (p1) with a Clark's level IV melanoma associated with recurrent cutaneous metastasis who subsequently experienced a complete remission after a period of therapy with dichloronitrobenzene (DCNB) and interferon-alpha (IFNalpha). Another patient (p2) with a similar Clark's level of disease but with a fatal prognosis and melanoma cells from the Sk-Mel 28 and MeWo cell lines served as control groups. Since cytokines and members of the alpha1 integrin family have been implicated in the growth and metastatic behaviour of melanomas, we evaluated the cytokine effects and integrins expressed by melanoma cells in the patients' tumours. P1, but not p2 nor MeWo melanoma cells, expressed HLA-DR, alpha1beta1 and the tumour necrosis factor receptor (TNF-R). Culturing p1 melanoma cells with TNFalpha, but not MeWo or p2 melanoma cells, increased their expression of alpha1beta1 integrin and was cytotoxic for the cells. Significant in vivo growth of metastatic p1 and p2 melanoma explants as well as MeWo cells grafted subcutaneously onto nude mice was noted over 36 days. Intralesional injection of TNFalpha induced complete regression of p1 explants, but not of p2 or MeWo explants. Intralesional injection of IFNalpha or anti-alpha1beta1 integrin arrested p1 graft growth. These results suggest that the slow growth of the melanoma cells in nude mice, as well as the susceptibility to tumour killing by TNFalpha and the dependence of the tumour on signals mediated by the alpha1beta1 integrin are features that may have contributed to the beneficial therapeutic response in patient 1.
Gilhar
A
A
The B. Rappaport Faculty of Medicine, Technion -Israel Institute of Technology, Haifa. Gilhar@techunix.technion.ac.il
Ullmann
Y
Y
Kalish
R S
RS
Berkutski
T
T
Azizi
E
E
Bank
I
I
D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D039222:Integrin alpha1beta1; D016023:Integrins / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000494:pharmacology; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D039222:Integrin alpha1beta1; D016023:Integrins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha